Sex differences in outcome after carotid revascularization in symptomatic and asymptomatic carotid artery stenosis.

OBJECTIVE: Sex differences regarding the safety and efficacy of carotid revascularization in carotid artery stenosis have been addressed in several studies with conflicting results. Moreover, women are underrepresented in clinical trials, leading to limited conclusions regarding the safety and efficacy of acute stroke treatments. METHODS: A systematic review and meta-analysis was performed by literature search including four databases from January 1985 to December 2021. Sex differences in the efficacy and safety of revascularization procedures, including carotid endarterectomy (CEA) and carotid artery stenting (CAS), for symptomatic and asymptomatic carotid artery stenoses were analyzed. RESULTS: Regarding CEA in symptomatic carotid artery stenosis, the stroke risk in men (3.6%) and women (3.9%) based on 99,495 patients (30 studies) did not differ (P = .16). There was also no difference in the stroke risk by different time frames up to 10 years. Compared with men, women treated with CEA had a significantly higher stroke or death rate at 4 months (2 studies, 2565 patients; 7.2% vs 5.0%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.04-2.12; I2 = 0%; P = .03), and a significantly higher rate of restenosis (1 study, 615; 17.2% vs 6.7%; OR, 2.81; 95% CI, 1.66-4.75; P = .0001). For CAS in symptomatic artery stenosis, data showed a non-significant tendency toward higher peri-procedural stroke in women, whereas for asymptomatic carotid artery stenosis, data based on 332,344 patients showed that women (compared with men) after CEA had similar rates of stroke, stroke or death, and the composite outcome stroke/death/myocardial infarction. The rate of restenosis at 1 year was significantly higher in women compared with men (1 study, 372 patients; 10.8% vs 3.2%; OR, 3.71; 95% CI, 1.49-9.2; P = .005). Furthermore, CAS in asymptomatic patients was associated with low risk of a postprocedural stroke in both sexes, but a significantly higher risk of in-hospital myocardial infarction in women than men (8445 patients, 1.2% vs 0.6%; OR, 2.01; 95% CI, 1.23-3.28; I2 = 0%; P = .005). CONCLUSIONS: A few sex-differences in short-term outcomes after carotid revascularization for symptomatic and asymptomatic carotid artery stenosis were found, although there were no significant differences in the overall stroke. This indicates a need for larger multicenter prospective studies to evaluate these sex-specific differences. More women, including those aged over 80 years, need to be enrolled in randomized controlled trials, to better understand if sex differences exist and to tailor carotid revascularization accordingly.

European Stroke Organisation guidelines on stroke in women: Management of menopause, pregnancy and postpartum.

Pregnancy, postpartum and menopause are regarded as periods women are more vulnerable to ischaemic events. There are conflicting results regarding stroke risk and hormone replacement therapy (HRT) during menopause. Stroke in pregnancy is generally increasing with serious consequences for mother and child; therefore, recommendations for acute treatment with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) are needed. The aim of this guideline is to support and guide clinicians in treatment decisions in stroke in women. Following the "Grading of Recommendations and Assessment, Development and Evaluation (GRADE)" approach, the guidelines were developed according to the European Stroke Organisation (ESO) Standard Operating Procedure. Systematic reviews and metanalyses were performed. Based on available evidence, recommendations were provided. Where there was a lack of evidence, an expert consensus statement was given. Low quality of evidence was found to suggest against the use of HRT to reduce the risk of stroke (ischaemic and haemorrhagic) in postmenopausal women. No data was available on the outcome of women with stroke when treated with HRT. No sufficient evidence was found to provide recommendations for treatment with IVT or MT during pregnancy, postpartum and menstruation. The majority of members suggested that pregnant women can be treated with IVT after assessing the benefit/risk profile on an individual basis, all members suggested treatment with IVT during postpartum and menstruation. All members suggested treatment with MT during pregnancy. The guidelines highlight the need to identify evidence for stroke prevention and acute treatment in women in more vulnerable periods of their lifetime to generate reliable data for future guidelines.

Vojta therapy improves postural control in very early stroke rehabilitation: a randomised controlled pilot trial.

BACKGROUND: It is still unclear, which physiotherapeutic approaches are most effective in stroke recovery. Vojta therapy is a type of physiotherapy that was originally developed for children and adolescents with cerebral palsy. Vojta therapy has been reported to improve automatic control of body posture. Because acute stroke patients are characterised by a disturbance in the ability to adapt to changes in body position, requiring automatic postural adjustment, we decided to investigate Vojta therapy in the early rehabilitation of stroke patients. Aim of the trial was to test the hypothesis that Vojta therapy - as a new physiotherapeutic approach in early stroke recovery - improves postural control and motor function in patients with acute ischaemic stroke (AIS) or intracerebral haemorrhage (ICH). METHODS: This prospective, randomised controlled trial included patients with imaging-confirmed AIS or ICH, severe hemiparesis and randomly assigned them to Vojta therapy or standard physiotherapy within 72 h after stroke onset. Main exclusion criterion was restricted ability to communicate. Primary endpoint was the improvement of postural control measured by the Trunk Control Test (TCT) on day 9 after admission. Secondary endpoint among others was improvement of arm function (measured with Motor Evaluation Scale for Upper Extremity in Stroke Patients [MESUPES]). RESULTS: Forty patients (20 per group) were randomised into the trial. Median age was 75 (66-80) years, 50% were women. The median improvement in TCT within 9 days was 25.5 points (=25.5%) (interquartile range [IQR] 12.5-42.5) in the Vojta group and 0 (IQR 0-13) in the control group (p = 0.001). Patients treated with Vojta therapy achieved a greater improvement in the MESUPES than patients in the control group (20% vs 10%, p = 0.006). CONCLUSION: This first randomised controlled trial of Vojta therapy in acute stroke patients demonstrates improvement of postural control through Vojta therapy compared to standard physiotherapy. Although this trial has some methodical weaknesses, Vojta therapy might be a promising approach in early stroke rehabilitation and should be studied in larger trials. TRIAL REGISTRATION: ClinicalTrials.gov; Unique identifier: NCT03035968. Registered 30 January 2017 - Retrospectively registered; http://www.clinicaltrials.gov.

Acute stroke in patients on new direct oral anticoagulants: how to manage, how to treat?

INTRODUCTION: For a long time, vitamin K antagonists (VKA) were the only available oral anticoagulants for clinical use. It is conceivable that the number of patients treated with novel direct oral anticoagulants (NOAC) will increase, due to the easy handling and the favorable risk-benefit profile compared with VKA. It is, therefore, expected that clinicians will be increasingly confronted with the question on how to treat acute ischemic stroke (AIS) if there is an indication for thrombolysis or how to manage intracranial bleedings. AREAS COVERED: In this review, we discuss controversies on thrombolysis in patients anticoagulated with NOAC, the dilemma of when to restart anticoagulation after AIS, and whether (and when) to re-institute oral anticoagulation after a brain hemorrhage. We provide suggestions for the management of these situations. EXPERT OPINION: Thrombolysis for patients with ischemic stroke who were given warfarin at subtherapeutic International normalized ratio values (≤ 1.7) may be considered according to guideline. Thrombolysis is contraindicated if intake of NOAC is reported in a patient, but no other information is available on-time of last intake of NOAC. Prothrombin complex concentrate have been proposed as a plausible, but unproven therapy to reverse the anticoagulant effects of NOACs.

Comparison of the European and Japanese guidelines for the acute management of intracerebral hemorrhage.

BACKGROUND: Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints: specific traditional and historical backgrounds and evidence-based medicine from modern randomized controlled trials (RCTs), meta-analysis and authorized clinical practice guidelines (GLs). Regarding intracerebral hemorrhage (ICH), Cerebrovascular Diseases published the 2006 European stroke initiative recommendations for the management of ICH. In 2009, the revised Japanese GLs for the management of stroke, including that of ICH, appeared in Japanese. Whereas GLs for the prevention and treatment of ischemic stroke were presented in detail, recommendations with regard to ICH are relatively rare both in Japan and Europe. METHODS: Since 2011, the authors have met repeatedly and have compared the latest versions of published European and Japanese GLs for ischemic and hemorrhagic strokes. Many aspects have only been addressed in one but left out in the other GLs, which consequently founded the basis for the comparison. Classification of evidence levels and recommendation grades defined by the individual committees differed between both original GLs. RESULTS: Aspects of major importance were similar and hence did not need extensive interpretation, mostly due to a lack of evidence from appropriate RCTs worldwide. The target level to which systolic blood pressure should be lowered is quite high; <170 mm Hg for patients with known hypertension in Europe and <180 mm Hg in Japan. The results of ongoing clinical trials are awaited for the optimal target level and optimal medications. Concerning ICH associated with oral anticoagulant therapy, both guidelines give similar recommendations, namely that anticoagulation should be discontinued and the international normalized ratio of prothrombin time should be normalized with prothrombin complex concentrate or fresh-frozen plasma and additional vitamin K. Patients with ICH were treated surgically, often based on individual decisions - more frequently in Japan, depending on the association with hypertension. Patients with large or intraventricular bleedings were only treated if a life-saving performance was considered, irrespective of the neurological outcome. Infra- and supratentorial differences were similarly addressed in both GLs. CONCLUSION: This brief survey - when compared with the lengthy original recommendations - provides a stimulating basis for an extended interest among Japanese and European stroke clinicians to learn from their individual experiences and to strengthen efforts for joint cooperation in treating and preventing stroke all around the globe.